Poison ivy/oak contact dermatitis is the most prevalent skin allergy in the United States, affecting >50% of the adult population. The condition is the major cause of occupational hazard among outdoor workers in forestry, agriculture and firefighting, resulting in significant medical expenses and workers disability. Attempts have been made to provide prophylactic treatment against this condition through administration of graduated doses of the plants'urushiols either orally or by injection with little success. The doses needed were usually very large and the protection afforded (if any) was short lived. During Phase I, we have developed a series of water soluble derivatives of the saturated isomers of urushiol and have shown that these derivatives, used as injectables, afforded complete protection from sensitization (tolerance) to the urushiols (poison ivy or oak) when administered to Naove guinea pigs;and prevented reaction to the urushiols when administered to already sensitive guinea pigs (desensitization). The goal of this Phase II application is to follow up on these exciting results of the phase I work and carry these products through a series of studies to select the most effective and safest product for further development into preclinical and clinical studies. Development of a feasible and economic synthetic route for the selected candidate, preliminary assessment of safety (lack of toxicity), determination of the optimum effective dose and assessment of the effect of booster dosing on the efficacy, as well as initiation of pharmacokinetics and metabolic studies are among the specific aims of this proposal. It is anticipated that at the end of this phase II project we will have a derivative that could be developed for the prevention and/or treatment of poison ivy contact dermatitis. This product will satisfy a medical need that is currently not being met by any such product on the market today. PUBLIC HEALTH RELEVANCE: This project is aimed at the development of a product for the prophylactic treatment of contact dermatitis caused by poison ivy and poison oak and other related plants. This product will satisfy currently unmet medical need. The extremely positive results of the phase I work promise a successful outcome of this phase II application.